Decrypting neuro-cancer crosstalk in pediatric cancers of the peripheral nervous system

Introduction

Cancer neuroscience has emerged as a major axis of cancer biology, at the crossroad of two biological areas. Multi-layered dialogs between cancer and nervous contingents have started to be unravelled, with pivotal roles of the nervous system in tumor initiation, growth, and invasion, in turn amplified by cancer-induced hijacking of nervous functions.

Brain Tumors and Neural Networks

Specifically, brain tumors were shown to be integrated in bona fide neuron-to-cancer synaptic networks but also to capture neural-activity dependent released factors that boost their tumor properties. In the last years, this completely rewired the view of high-grade gliomas, especially those arising in the pediatric population, suggesting specific vulnerabilities when neural networks are being shaped.

Neuro-Cancer Crosstalk in the PNS

The knowledge regarding neuro-cancer crosstalk in the peripheral nervous system (PNS) is far more fragmented and is even obscure in malignancies arising within peripheral nervous tissues. Neuroblastoma (NB) is an emblematic, deadly, pediatric cancer of the PNS, with primary tumors that develop in sympathetic ganglia or in the adrenal gland.

Impact of Neural Activity on NB

Despite its occurrence in sites of active central-to-PNS synaptic contacts, whether neural activity impacts on NB tumor features and metastatic progression is fully unknown.

Proposed Model and Objectives

We have conceived a model of NB that reproduces the embryonic and nervous microenvironment in which it arises but also the sequence of its metastatic progression. Guided by preliminary data, the objective of the proposal is to decrypt the panel of neuro-cancer functional interplays in NB, at the anatomical, electrophysiological, and molecular level.

Methodology and Aims

We will deploy multidisciplinary and cutting-edge approaches to provide a comprehensive and dynamic picture of neuro-NB dialogs, in relevant models for this pediatric cancer. Our underlying aims are to:

1. Identify novel entry points for therapeutic strategies.
2. Define subtypes of NB that would benefit from neuro-related therapies.